Abstract
Triplebodies are antibody-derived recombinant proteins carrying 3 antigen-binding domains in a single polypeptide chain. Triplebody SPM-1 was designed for lysis of CD19-bearing malignant B-lymphoid cells through the engagement of CD16-expressing cytolytic effectors, including NK and gd T cells. SPM-1 is an optimized version of triplebody ds(19-16-19) and includes humanization, disulfide stabilization and the removal of potentially immunogenic sequences. A three-step chromatographic procedure yielded 1.7 - 5.5 mg of purified, monomeric protein per liter of culture medium. In cytolysis assays with NK cell effectors, SPM-1 mediated potent lysis of cancer-derived B cell lines and primary cells from patients with various B-lymphoid malignancies, which surpassed the ADCC activity of the therapeutic antibody Rituximab. EC50-values ranged from 3 to 86 pM. Finally, in an impedance-based assay, SPM-1 mediated a particularly rapid lysis of CD19-bearing target cells by engaging and activating both primary and expanded human gd T cells from healthy donors as effectors. These data establish SPM-1 as a useful tool for a kinetic analysis of the cytolytic reactions mediated by gd T and NK cells and as an agent deserving further development towards clinical use for the treatment of B-lymphoid malignancies.
| Item Type: | Journal article |
|---|---|
| Faculties: | Biology > Department Biology II Medicine |
| Subjects: | 500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine and health |
| ISSN: | 1949-2553 |
| Language: | English |
| Item ID: | 48705 |
| Date Deposited: | 27. Apr 2018, 08:16 |
| Last Modified: | 04. Nov 2020, 13:26 |
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